bims-caglex 2024-03-10 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2024–03–10
ten papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

An Antibody-directed and Immune Response Modifier-augmented Photothermal Therapy Strategy Relieves Aging via Rapid Immune Clearance of Senescent Cells.
Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases.
Organ-specific biological clocks: ageotyping for personalized anti-aging medicine.
The long and winding road of reprogramming-induced rejuvenation.
How calorie restriction slows aging: an epigenetic perspective.
Exploring the emerging bidirectional association between inflamm-aging and cellular senescence in organismal aging and disease.
Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.
Cellular senescence and wound healing in aged and diabetic skin.
A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.
Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes.

Aging Dis. 2024 Apr 01. 15(2): 787-803

An Antibody-directed and Immune Response Modifier-augmented Photothermal Therapy Strategy Relieves Aging via Rapid Immune Clearance of Senescent Cells.

Jiamei Han, Judun Zheng, Qian Li, Huanle Hong, Jing Yao, Jiao Wang, Robert Chunhua Zhao.

Cellular senescence is an irreversible and multifaceted process inducing tissue dysfunction and organismal aging, and thus the clearance of senescent cells can prevent or delay the onset of aging-related pathologies. Herein, we developed an augmented photothermal therapy strategy integrated with an antibody against β2-microglobulin (aB2MG) and an immune adjuvant imiquimod (R837) to effectively accelerate senescent cell apoptosis and clearance under a near-infrared light. With this strategy, the designed CroR@aB2MG enables the targeting of senescent cells and the application of photothermal therapy concomitantly, the initiation of immune clearance subsequently, and finally the realization of protective effects against senescence. Our results showed that the photo-induced heating effect caused senescent cells to quickly undergo apoptosis and the synchronous immune response accelerated the clearance of senescent cells in vitro and in vivo. Therefore, this photoactivated speedy clearing strategy may provide an efficient way for the treatment of senescence-related diseases by eliminating senescent cells with biomaterials.

DOI: https://doi.org/10.14336/AD.2023.0628-1
J Nat Prod. 2024 Mar 04.

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases.

Mazzarine Dotou, Aurore L'honoré, Roba Moumné, Chahrazade El Amri.

Nature is an important source of bioactive compounds and has continuously made a large contribution to the discovery of new drug leads. Particularly, plant-derived compounds have long been identified as highly interesting in the field of aging research and senescence. Many plants contain bioactive compounds that have the potential to influence cellular processes and provide health benefits. Among them, Piper alkaloids have emerged as interesting candidates in the context of age-related diseases and particularly senescence. These compounds have been shown to display a variety of features, including antioxidant, anti-inflammatory, neuroprotective, and other bioactive properties that may help counteracting the effects of cellular aging processes. In the review, we will put the emphasis on piperlongumine and other related derivatives, which belong to the Piper alkaloids, and whose senomodulating potential has emerged during the last several years. We will also provide a survey on their potential in therapeutic perspectives of age-related diseases.

DOI: https://doi.org/10.1021/acs.jnatprod.3c01195
Ageing Res Rev. 2024 Mar 04. pii: S1568-1637(24)00071-0. [Epub ahead of print] 102253

Organ-specific biological clocks: ageotyping for personalized anti-aging medicine.

Francesco Prattichizzo, Chiara Frigé, Valeria Pellegrini, Lucia Scisciola, Aurelia Santoro, Daniela Monti, Maria Rita Rippo, Mikhail Ivanchenko, Fabiola Olivieri, Claudio Franceschi.

  Aging is a complex multidimensional, progressive remodeling process affecting multiple organ systems. While many studies have focused on studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is a cutting-edge issue. An organ's biological age might influence the aging of other organs, revealing a multiorgan aging network. Recent data demonstrated a similar yet asynchronous inter-organs and inter-individuals progression of aging, thereby providing a foundation to track sources of declining health in old age. The integration of multiple omics with common clinical parameters through artificial intelligence has allowed the building of organ-specific aging clocks, which can predict the development of specific age-related diseases at high resolution. The peculiar individual aging-trajectory, referred to as ageotype, might provide a novel tool for a personalized anti-aging, preventive medicine. Here, we review data relative to biological aging clocks and omics-based data, suggesting different organ-specific aging rates. Additional research on longitudinal data, including young subjects and analyzing sex-related differences, should be encouraged to apply ageotyping analysis for preventive purposes in clinical practice.

Keywords:  age-related diseases; ageotypes; biological clock; cardiovascular diseases; frailty; inflammaging; omics

DOI:  https://doi.org/10.1016/j.arr.2024.102253
Nat Commun. 2024 Mar 02. 15(1): 1941

The long and winding road of reprogramming-induced rejuvenation.

Ali Doğa Yücel, Vadim N Gladyshev.

Organismal aging is inherently connected to the aging of its constituent cells and systems. Reducing the biological age of the organism may be assisted by reducing the age of its cells - an approach exemplified by partial cell reprogramming through the expression of Yamanaka factors or exposure to chemical cocktails. It is crucial to protect cell type identity during partial reprogramming, as cells need to retain or rapidly regain their functions following the treatment. Another critical issue is the ability to quantify biological age as reprogrammed older cells acquire younger states. We discuss recent advances in reprogramming-induced rejuvenation and offer a critical review of this procedure and its relationship to the fundamental nature of aging. We further comparatively analyze partial reprogramming, full reprogramming and transdifferentiation approaches, assess safety concerns and emphasize the importance of distinguishing rejuvenation from dedifferentiation. Finally, we highlight translational opportunities that the reprogramming-induced rejuvenation approach offers.

DOI: https://doi.org/10.1038/s41467-024-46020-5
J Mol Med (Berl). 2024 Mar 08.

How calorie restriction slows aging: an epigenetic perspective.

Gyeong Min Lim, Nagarajan Maharajan, Gwang-Won Cho.

  Genomic instability and epigenetic alterations are some of the prominent factors affecting aging. Age-related heterochromatin loss and decreased whole-genome DNA methylation are associated with abnormal gene expression, leading to diseases and genomic instability. Modulation of these epigenetic changes is crucial for preserving genomic integrity and controlling cellular identity is important for slowing the aging process. Numerous studies have shown that caloric restriction is the gold standard for promoting longevity and healthy aging in various species ranging from rodents to primates. It can be inferred that delaying of aging through the main effector such as calorie restriction is involved in cellular identity and epigenetic modification. Thus, an understanding of aging through calorie restriction may seek a more in-depth understanding. In this review, we discuss how caloric restriction promotes longevity and healthy aging through genomic stability and epigenetic alterations. We have also highlighted how the effectors of caloric restriction are involved in modulating the chromatin-based barriers.

Keywords:  Aging; Caloric restriction; Chromosome stability; Epigenetic; Sirt1

DOI:  https://doi.org/10.1007/s00109-024-02430-y
Cell Biochem Funct. 2024 Mar;42(2): e3970

Exploring the emerging bidirectional association between inflamm-aging and cellular senescence in organismal aging and disease.

Rohit Sharma.

  There is strong evidence that most individuals in the elderly population are characterized by inflamm-aging which refers to a subtle increase in the systemic pro-inflammatory environment and impaired innate immune activation. Although a variety of distinct factors are associated with the progression of inflamm-aging, emerging research is demonstrating a dynamic relationship between the processes of cellular senescence and inflamm-aging. Cellular senescence is a recognized factor governing organismal aging, and through a characteristic secretome, accumulating senescent cells can induce and augment a pro-inflammatory tissue environment that provides a rationale for immune system-independent activation of inflamm-aging and associated diseases. There is also accumulating evidence that inflamm-aging or its components can directly accelerate the development of senescent cells and ultimately senescent cell burden in tissues in a likely vicious inflammatory loop. The present review is intended to describe the emerging senescence-based molecular etiology of inflamm-aging as well as the dynamic reciprocal interactions between inflamm-aging and cellular senescence. Therapeutic interventions concurrently targeting cellular senescence and inflamm-aging are discussed and limitations as well as research opportunities have been deliberated. An effort has been made to provide a rationale for integrating inflamm-aging with cellular senescence both as an underlying cause and therapeutic target for further studies.

Keywords:  aging; cellular senescence; inflamm-aging; inflammation; senescent cells

DOI:  https://doi.org/10.1002/cbf.3970
Biogerontology. 2024 Mar 04.

Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.

Kento Takaya, Kazuo Kishi.

  Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin.

Keywords:  ENPP5; Knockdown; Rejuvenation; SASP; Skin aging

DOI:  https://doi.org/10.1007/s10522-024-10096-9
Front Physiol. 2024 ;15 1344116

Cellular senescence and wound healing in aged and diabetic skin.

Arisa Kita, Sena Yamamoto, Yuki Saito, Takako S Chikenji.

  Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects.

Keywords:  aged-skin; cellular senescence; diabetic skin; senescence-associated secretory phenotypes (SASP); woundhealing

DOI:  https://doi.org/10.3389/fphys.2024.1344116
Aging Cell. 2024 Mar 07. e14104

A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.

Shruthi Hamsanathan, Tamil Anthonymuthu, Denise Prosser, Anna Lokshin, Susan L Greenspan, Neil M Resnick, Subashan Perera, Satoshi Okawa, Giri Narasimhan, Aditi U Gurkar.

  Unlike chronological age, biological age is a strong indicator of health of an individual. However, the molecular fingerprint associated with biological age is ill-defined. To define a high-resolution signature of biological age, we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and the interaction between them, from a cohort of healthy and rapid agers. The balance between two fatty acid oxidation mechanisms, β-oxidation and ω-oxidation, associated with the extent of functional aging. Furthermore, a panel of 25 metabolites, Healthy Aging Metabolic (HAM) index, predicted healthy agers regardless of gender and race. HAM index was also validated in an independent cohort. Causal inference with machine learning implied three metabolites, β-cryptoxanthin, prolylhydroxyproline, and eicosenoylcarnitine as putative drivers of biological aging. Multiple SASP markers were also elevated in rapid agers. Together, our findings reveal that a network of metabolic pathways underlie biological aging, and the HAM index could serve as a predictor of phenotypic aging in humans.

Keywords:  SASP; aging; biological age; cellular senescence; metabolomics

DOI:  https://doi.org/10.1111/acel.14104
Curr Opin Oncol. 2024 Mar 01. 36(2): 82-92

Epigenetic dynamics of aging and cancer development: current concepts from studies mapping aging and cancer epigenomes.

Shilpa Bisht, Yiqing Mao, Hariharan Easwaran.

PURPOSE OF REVIEW: This review emphasizes the role of epigenetic processes as incidental changes occurring during aging, which, in turn, promote the development of cancer.
RECENT FINDINGS: Aging is a complex biological process associated with the progressive deterioration of normal physiological functions, making age a significant risk factor for various disorders, including cancer. The increasing longevity of the population has made cancer a global burden, as the risk of developing most cancers increases with age due to the cumulative effect of exposure to environmental carcinogens and DNA replication errors. The classical 'somatic mutation theory' of cancer cause is being challenged by the observation that multiple normal cells harbor cancer driver mutations without resulting in cancer. In this review, we discuss the role of age-associated epigenetic alterations, including DNA methylation, which occur across all cell types and tissues with advancing age. There is an increasing body of evidence linking these changes with cancer risk and prognosis.
SUMMARY: A better understanding about the epigenetic changes acquired during aging is critical for comprehending the mechanisms leading to the age-associated increase in cancer and for developing novel therapeutic strategies for cancer treatment and prevention.

DOI: https://doi.org/10.1097/CCO.0000000000001020